Idazoxan and Response to Typical Neuroleptics in Treatment-Resistant Schizophrenia: Comparison with the Atypical Neuroleptic, Clozapine

Background. We investigated whether antagonism of α₂ adrenergic receptors would augment treatment response in schizophrenia, by administering idazoxan, an α₂ antagonist drug, to treatment-resistant patients on typical neuroleptics. Method. Seventeen hospitalised treatment-resistant patients with DSM-III-R schizophrenia or schizoaffective disorder were studied on typical neuroleptic treatment, on treatment with idazoxan plus typical neuroleptic, and after discontinuation of idazoxan, in fixed, non-random order, and under double-blind, placebo-controlled conditions. Results. The addition of idazoxan to fluphenazine treatment resulted in significant reductions of global psychosis and total, positive and negative symptoms on the Brief Psychiatric Rating Scale, compared to neuroleptic treatment alone. Symptom improvement significantly correlated with idazoxan-induced changes in indices of noradrenergic function. In a subgroup of patients, idazoxan plus typical neuroleptic treatment compared favourably with clozapine treatment, when both were compared to typical neuroleptic treatment alone. Conclusions. The antagonism of α₂ receptors augmented therapeutic response to typical neuroleptic treatment in treatment-resistant patients with schizophrenia. This antagonism may contribute to clozapine's superior antipsychotic effects.